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PMID: 15161652 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Kinetics of gene expression in murine cutaneous graft-versus-host disease.

The American journal of pathology ·Vol. 164 ·No. 6 ·2004-06-00 ·Pages 2189-202

Sugerman PB, Faber SB, Willis LM, Petrovic A, Murphy GF, Pappo J, Silberstein D, van den Brink MR

Abstract

The kinetics of gene expression associated with the development of cutaneous graft-versus-host disease (GVHD) were examined in a mouse model of MHC-matched allogeneic hematopoietic stem cell transplantation. Ear skin was obtained from recipient mice with or without GVHD between 7 and 40 days after transplantation for histopathological analysis and gene expression profiling. Gene expression patterns were consistent with early infiltration and activation of CD8(+) T and mast cells, followed by CD4(+) T, natural killer, and myeloid cells. The sequential infiltration and activation of effector cells correlated with the histopathological development of cutaneous GVHD and was accompanied by up-regulated expression of many chemokines and their receptors (CXCL-1, -2, -9, and -10; CCL-2, -5, -6, -7, -8, -9, -11, and -19; CCR-1 and CCR-5), adhesion molecules (ICAM-1, CD18, Ly69, PSGL-1, VCAM-1), molecules involved in antigen processing and presentation (TAP1 and TAP2, MHC class I and II, CD80), regulators of apoptosis (granzyme B, caspase 7, Bak1, Bax, and BclII), interferon-inducible genes (STAT1, IRF-1, IIGP, GTPI, IGTP, Ifi202A), stimulators of fibroblast proliferation and matrix synthesis (interleukin-1beta, transforming growth factor-beta1), and markers of keratinocyte proliferation (keratins 5 and 6), and differentiation (small proline-rich proteins 2E and 1B). Many acute-phase proteins were up-regulated early in murine cutaneous GVHD including serum amyloid A2 (SAA2), SAA3, serpins a3g and a3n, secretory leukocyte protease inhibitor, and metallothioneins 1 and 2. The kinetics of gene expression were consistent with the evolution of cutaneous pathology as well as with current models of disease progression during cutaneous GVHD.

MeSH Terms
Animals Chemokines/genetics Disease Models, Animal Enzyme-Linked Immunosorbent Assay Gene Expression Profiling Gene Expression Regulation/genetics Graft vs Host Disease/genetics,pathology Kinetics Major Histocompatibility Complex Mice Receptors, Chemokine/genetics Skin/pathology Stem Cell Transplantation/adverse effects
Chemicals
Chemokines Receptors, Chemokine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sugerman Philip B
straZeneca Research and Development Boston, Waltham, Massachusetts, USA.
Faber Sara B
Willis Lucy M
Petrovic Aleksandra
Murphy George F
Pappo Jacques
Silberstein David
van den Brink Marcel R M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63776-5
Published
2004-06-00
Pages
2189-202
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1615752
Subset
IM
Grants
NCI NIH HHS · CA40358 · United States
NHLBI NIH HHS · HL69929 · United States
NHLBI NIH HHS · R01 HL069929 · United States
NHLBI NIH HHS · R01 HL072412 · United States
NHLBI NIH HHS · HL72412 · United States
NCI NIH HHS · R01 CA040358 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63776-5 PMC Full Text View journal details
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